Liu Yunxian, Hilakivi-Clarke Leena, Zhang Yukun, Wang Xiao, Pan Yuan-Xiang, Xuan Jianhua, Fleck Stefanie C, Doerge Daniel R, Helferich William G
Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, IL, USA.
Department of Oncology, Georgetown University Medical Center, Washington, DC, USA.
Mol Nutr Food Res. 2015 Aug;59(8):1419-30. doi: 10.1002/mnfr.201500028. Epub 2015 Jun 26.
Soy flour diet (MS) prevented isoflavones from stimulating MCF-7 tumor growth in athymic nude mice, indicating that other bioactive compounds in soy can negate the estrogenic properties of isoflavones. The underlying signal transduction pathways to explain the protective effects of soy flour consumption were studied here.
Ovariectomized athymic nude mice inoculated with MCF-7 human breast cancer cells were fed either Soy flour diet (MS) or purified isoflavone mix diet (MI), both with equivalent amounts of genistein. Positive controls received estradiol pellets and negative controls received sham pellets. GeneChip Human Genome U133 Plus 2.0 Array platform was used to evaluate gene expressions, and results were analyzed using bioinformatics approaches. Tumors in MS-fed mice exhibited higher expression of tumor growth suppressing genes ATP2A3 and BLNK and lower expression of oncogene MYC. Tumors in MI-fed mice expressed a higher level of oncogene MYB and a lower level of MHC-I and MHC-II, allowing tumor cells to escape immunosurveillance. MS-induced gene expression alterations were predictive of prolonged survival among estrogen-receptor-positive breast cancer patients, whilst MI-induced gene changes were predictive of shortened survival.
Our findings suggest that dietary soy flour affects gene expression differently than purified isoflavones, which may explain why soy foods prevent isoflavones-induced stimulation of MCF-7 tumor growth in athymic nude mice.
大豆粉饮食(MS)可防止异黄酮刺激无胸腺裸鼠体内MCF-7肿瘤生长,这表明大豆中的其他生物活性化合物可抵消异黄酮的雌激素特性。本文研究了解释食用大豆粉保护作用的潜在信号转导途径。
给接种了MCF-7人乳腺癌细胞的去卵巢无胸腺裸鼠喂食大豆粉饮食(MS)或纯化异黄酮混合饮食(MI),二者的染料木黄酮含量相等。阳性对照接受雌二醇植入物,阴性对照接受假植入物。使用基因芯片人类基因组U133 Plus 2.0阵列平台评估基因表达,并采用生物信息学方法分析结果。喂食MS的小鼠肿瘤中,肿瘤生长抑制基因ATP2A3和BLNK的表达较高,癌基因MYC的表达较低。喂食MI的小鼠肿瘤中,癌基因MYB的表达水平较高,MHC-I和MHC-II的水平较低,这使得肿瘤细胞能够逃避免疫监视。MS诱导的基因表达改变可预测雌激素受体阳性乳腺癌患者的生存期延长,而MI诱导的基因改变则可预测生存期缩短。
我们的研究结果表明,膳食大豆粉对基因表达的影响与纯化异黄酮不同,这可能解释了为什么大豆食品可防止异黄酮诱导的无胸腺裸鼠体内MCF-7肿瘤生长。